The effect of a traditional Chinese quadri-combination therapy and its component quercetin on recurrent spontaneous abortion: A clinical trial, network pharmacology and experiments-based study

Abstract

Objective: To explore the effect and mechanisms of a traditional Chinese quadri-combination therapy [Bushen, Yiqi, Lixue and Yangtai (BYLY)] in treating recurrent spontaneous abortion (RSA).Methods: A clinical trial was conducted to study the effect of BYLY on RSA. Pharmacological network analysis and UPLC-Q/TOF-mass spectrometry (MS) were applied to investigate the key active component in BYLY and potential targets. Cellular experiments based on former results were performed to examine the mechanism of BYLY in the treatment of RSA.Results: Four hundred and eighty participants enrolled in the clinical trial. The results showed that, compared with the use of BYLY or duphaston alone, a combination of duphaston and BYLY could decrease the early abortion rate in RSA (p < 0.001). Network pharmacological analysis indicated that BYLY contained 132 active components and 146 core targets, and the quercetin maybe the key effective component. In vitro experiments found that pretreatment of quercetin at the correct concentration (2 μM) prevented hypoxia-induced viability and proliferation reduction, and apoptosis and mitochondrial dysfunction. Furthermore, quercetin could modulate mitochondrial fission/fusion balance in trophoblasts, and specifically decrease the expression of Drp1 by regulating miR-34a-5p.Conclusion: BYLY could improve pregnancy outcomes of RSA, based on multi-components and multi-targets. The protective effect of quercetin on trophoblasts, through decreasing Drp1 expression via regulating miR-34a-5p, might be one possible effective mechanism.

Protective effect of quercetin on lipopolysaccharide‑induced miscarriage based on animal experiments and network pharmacology

“…Moreover, cao et al (59) found that quercetin counteracted hyperglycemia-induced nitrosative stress and oxidative stress, decreased the levels of oxidative stress markers and increased the expression of superoxide dismutase 1 and 2 and ultimately reduced the rate of embryonic malformations in diabetic pregnant mice. in addition, in vitro experiments have demonstrated that quercetin at appropriate concentrations can improve biological function, mitochondrial membrane potential and morphology of trophoblast cells under hypoxic conditions (60). decidual natural killer (nK) cells are the primary immune cell population at the maternal-fetal interface, with low cytotoxicity (61), which enhance decidual cell invasion as well as spiral artery remodeling through the secretion of matrix metalloproteinases, vascular endothelial growth factor and interleukins, regulating maternal-fetal immune tolerance and placental developmental capacity (62)(63)(64)(65).…”

Effect of Chinese patent medicine Kunling Pill on endometrial receptivity: A clinical trial, network pharmacology, and animal-based study

“…The composition of TCM is complex; all kinds of Chinese medicine often have some similar chemical components, so the search for the main effective components will help to analyze the key points of Chinese medicine in treating diseases and provide direction for the follow-up molecular mechanism. Network pharmacology, a biological system analysis approach, was utilized to uncover the relationship between multi-component medicines and the network target of diseases (20)(21). The topological analysis found twenty key targets of KLP, including TP53, ESR1, EGFR, MAPK3, AKT1, TNF, STAT3, CTNNB1, IL6, HIF1A, MYC, FOS, PTGS2, MMP9, CCND1, IL1β, HSP90AA1, PTEN, CXCL8, and IL10.…”

Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications—A Review

“…In this regard, four hundred and eighty participants were assigned to the clinical trial, it was shown that combined duphaston and BYLY could decrease the rate of early abortion compared with the use of duphaston or BYLY alone. It is believed that a possible mechanism is the protective effect of quercetin on trophoblasts by decreasing Drp1 expression through regulating miR-34a-5p [112]. In another randomized, doubleblind, placebo-controlled trial using quercetin for two weeks, the results revealed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) were decreased by 50.4%, 37.2%, and 89.9%, respectively.…”